1. Field of the Invention
The present invention relates to an implant for use in the repair, replacement and/or augmentation of tissue, including various portions of animal or human skeletal systems, and to a method for manufacturing the implant. More particularly, this invention relates to an implant made up of a solid aggregate of bone-derived elements, the manufacture of the implant and its use in the repair of bone defects.
2. Description of the Related Art
The use of autograft bone, allograft bone or xenograft bone is well known in both human and veterinary medicine. See Stevenson et al., Clinical Orthopedics and Related Research, 323, pp. 66-74 (1996); Buttermann et al., xe2x80x9cThe Use of bone allografts in the spinexe2x80x9d, Clinical Orthopedics and Related Research, 324, pp.75-85 (1996). In particular, transplanted bone is known to provide support, promote healing, fill bony cavities, separate bony elements such as vertebral bodies, promote fusion and stabilize the sites of fractures. More recently, processed bone has been developed into shapes for use in new surgical applications, or as new materials for implants that were historically made of non-biologically derived materials.
Bone is made of several endogenous constituents, including collagen, hydroxyapatite and several active proteins. When used as a biomaterial, these components of the bone can provide advantageous biological and mechanical properties. Such properties may be enhanced by processing treatments and/or the addition of one or more medically useful substances to the bone.
Allograft bone has been demonstrated, over the course of several decades, to provide significant clinical advantages in the treatment of certain orthopedic, podiatric, oral, maxillofacial, dental, and other skeletal diseases. Unlike other implants used in skeletal sites, allograft bone implants have the capacity to participate in bony healing at the site of surgery, through the events of callous formation and wound healing, and osteonal remodeling. Cortical allograft implants, however, remodel slowly over the course of months to years, and all bone allografts have been limited to shapes and sizes dictated by the limits of the initial starting bone tissue.
One known type of allograft bone implant involves treatment of the bone with gluteraldehyde and/or proteoglycan removal in order to induce calcification in the implant. This treated implant is then placed in a solution of simulated body fluid so as to induce calcification. See Nimni et al., xe2x80x9cCollagenxe2x80x9d, Vol 3, Biotechnology, pp.20-23, CRC Press, Boca Raton, Fla. (1998).
U.S. Pat. No. 5,899,939 describes a bone-derived implant made up of one or more layers of fully mineralized or partially demineralized cortical bone which are assembled into a unitary structure to provide an implant exhibiting good overall load-supporting properties.
U.S. Pat. No. 6,123,731 describes an implant fabricated from a solid aggregate of bone-derived elements possessing chemical linkages between their adjacent surface-exposed collagen. Other components can be incorporated into the bone implant material such as bone-growth inducing substances, growth factors, etc.
The present invention provides an implant which can potentially utilize the natural healing capacities of bone tissue and which can be formed with a range of geometries, internal porosity and architectures. The advantageous features of the implant include the ability to approximate the internal architecture and porosity of natural bone thereby providing the capability to improve the biological healing response. Implants with allograft properties can be made to shapes and sizes that are not limited by the geometry of the bone from which they are made and can provide a stock material for subsequent shaping to fit a particular bone repair site.
It is an object of the invention to provide an implant made up of bone-derived elements that are made to adhere to each other so as to provide a solid aggregate whose mechanical and biological properties approach those of healthy bone.
It is a particular object of the present invention to provide an implant made up of a solid aggregate of bone-derived elements which are bonded to each other through their engagement with a biocompatible nonadhesive binding agent.
It is another object of this invention to provide an implant which can optionally include one or more medically/surgically useful substances such as bone-growth inducing substances, growth factors, etc.
It is yet another object of the invention to provide an implant possessing a network of pores, perforations, apertures, channels or spaces which permits and encourages penetration by endogenous and exogenous bone healing materials and blood supply, and simultaneously provides a means for incorporating one or more bone healing substances.
It is still a further object of the present invention to provide an implant which can be fashioned into a variety of shapes and sizes which are not limited by constraints imposed by the size and/or types of donor bone which are available for the construction of the implant.
It is also an object of the invention to provide a method of manufacturing an implant which will provide a strong, biocompatible implant of any size and/or shape for implantation.
In keeping with these and other objects of the invention, there is provided an implant which comprises a solid aggregate of bone-derived elements in which the surfaces of individual bone-derived elements possess one or more binding agents selected from the group consisting of metal oxide, metal hydroxide, metal salt of an inorganic acid, metal salt of an organic acid and metal-containing silica-based glass, the binding agent possessing at least slight solubility in a polar solvent, adjacent bone-derived elements in the aggregate being bonded to each other through engagement with the binding agent.
Further in keeping with the invention, there is provided a method of making an implant made up of a solid aggregate of bone-derived elements which comprises:
a) contacting the surfaces of a quantity of bone-derived elements with a polar solvent solution of binding agent selected from the group consisting of metal oxide, metal hydroxide, metal salt of an inorganic acid, metal salt of an organic acid and metal-containing silica-based glass.
b) forming the bone-derived elements into an aggregate prior to or following contacting step (a); and,
c) removing polar solvent from the aggregate of bone-derived elements to provide the implant, the surfaces of individual bone-derived elements in the implant possessing binding agent with adjacent bone-derived elements being bonded to each other through engagement with the binding agent.
The implant of this invention is intended to be used in the repair of any of a variety of bone defects where it can facilitate healing through one or more osteogenic, osteoconductive and/or osteoinductive mechanisms. The bone-derived implant, or osteoimplant, of the present invention can be made to approximate the mechanical strength characteristics of natural bone and to permit gradual transfer of load-bearing support therefrom to newly formed bone tissue over time.
The term xe2x80x9costeogenicxe2x80x9d as used herein shall be understood to refer to the ability of a substance to induce new bone formation via the participation of living cells from within the substance.
The term xe2x80x9costeoconductivexe2x80x9d as used herein shall be understood to refer to the ability of a substance or material to provide surfaces that are receptive to the growth of new host bone.
The term xe2x80x9costeoinductivexe2x80x9d as used herein shall be understood to refer to the ability of a substance to recruit cells from the host which have osteogenic potential and the ability to form ectopic bone.
The expression xe2x80x9cbone-derived elementsxe2x80x9d as used hereinafter shall be understood to refer to pieces of bone in any of a variety of sizes, thicknesses and configurations, including monolithic segments of bone, thin to thick bone sheets and smaller pieces of bone such as powders, particles, granules, fibers, strips, etc., which can be obtained by milling, slicing, cutting or machining whole bone. Such elements can be fully mineralized, partially demineralized or fully demineralized.
The term xe2x80x9cbiocompatiblexe2x80x9d and expressions of like import shall be understood to mean the absence of unacceptable detrimental biological response, e.g., stimulation of a severe, long-lived or escalating biological response to an implant and is distinguished from a mild, transient inflammation which accompanies implantation of essentially all foreign objects into a living organism and is also associated with the normal healing response. Thus, materials which alone in appropriate quantities are generally considered nonbiocompatible can be considered biocompatible within the aforestated meaning if present in small enough quantities such that they do not elicit a significant level of undesirable or detrimental tissue response.
The term xe2x80x9cengagementxe2x80x9d is used herein to define the nature of the bonding of adjacent bone-derived particles as achieved either by the interlocking of mutually contacting particles of binding agent present on the surfaces of adjacent bone-derived elements and/or by bridge-like structures of binding agent spanning gaps between adjacent bone-derived elements. Accordingly, the engagement of adjacent bone-derived elements with the binding agent in accordance with the present invention can be thought of as largely mechanical in nature. Specific preferred examples include inter-element crystalline bridges induced either by precipitation reaction or by solid state crystal nucleation.
The term xe2x80x9cnonadhesivexe2x80x9d shall be understood to exclude known and conventional xe2x80x9cadhesivesxe2x80x9d, the latter term being reserved for materials that achieve bonding of substrates primarily by means of electrical forces, molecular forces such as van der Waals forces or diffusion into the substrates, e.g. as is the case with the in situ formed acrylate adhesives that heretofore have been used in the making and/or installation of implants for the repair of bone defects. Examples of non-adhesive biocompatible binding agents include crystalline calcium phosphates such as hydroxyapatite, poorly crystalline hydroxyapatite or dicalcium phosphate dihydrate each of which is among the useful binding agents herein.
The expression xe2x80x9cendogenous binding agentxe2x80x9d refers to a generally crystalline binding agent produced when salts endogenous to bone are induced to recrystallize as the same salt, or a different phase of the same material, or as a precipitate following a reaction between an exogenous and an endogenous material. Such recrystallizations may be solvent-mediated or occur in the solid phase.